Sequence-specific activators stimulate transcription by communicating with various factors to activates transcription. Biochemical studies of eukaryotic transcriptional activation demonstrate both physical and functional interactions of activators with various components of RNA polymerase II transcriptional machinery that in turn facilitate pre-initiation complex assembly and function. Among these factors, TAF subunits of TFIID are shown to be important cofactors which mediate activated transcription by providing interaction sites for distinct activators. In addition to this direct connection to the transcription machinery, various activators bind to coactivators such as p300/CBP. p300/CBP is a large protein consisting of over 2,400 amino acids, known to interact with a variety of DNA-binding transcriptional factors including nuclear hormone receptors, CREB, c-Jun, c-Myb, Sap-1a, c-Fos and MyoD. Furthermore, p300/CBP recruits coactivators PCAF and ACTR to activate transcription. We demonstrated that PCAF, p300, CBP, ACTR and TAFII250 all have intrinsic histone acetylase activity. These findings suggest that targeted histone acetylation at specific promoters may be involved in mechanisms by which RNA polymerase II transcriptional machinery gains access to transcriptionally repressed chromatin.